The Molecular Culprits Underlying Precocious Mammary Gland Involution

Mammary gland involution, characterized by extensive apoptosis and structural remodelling of the gland, is the process by which the gland is returned to the pre-pregnant state. A key advantage of the mammary gland is the ability to synchronize involution through forced weaning, thus allowing the dissection of biochemical pathways involved in the involution process. Over the past few years, significant advances have been made in understanding the signaling pathways and downstream effectors that regulate epithelial cell apoptosis in the first phase of involution, and the importance of matrix metalloproteinases and their inhibitors in both phases of involution. The precise nature of the triggers for apoptosis, however, and the ultimate perpetrators of cell death are not yet clear. This review focuses on genes whose perturbation, either by targeted deletion or overexpression in transgenic mouse models, leads to precocious involution. The accumulating data point to a complex network of signal transduction pathways that synergize to regulate apoptosis in the involuting mammary gland.